Joe Hirsch of the Daily Racing Form wrote: "Every time he ran he was an odds-on favorite, and the response to his presence on the racetrack, either for a morning workout or a major race, was electric. 'Slewmania' was a virulent and widespread condition."[2]

Horse owners since the early 1970s, Karen Taylor was a former flight attendant, and her husband, Mickey Taylor, was a lumberman. They lived in White Swan, Washington. Their friend Dr. Jim Hill, a veterinarian, recommended that they buy Seattle Slew, a son of Bold Reasoning out of the mare My Charmer, at a 1975 Fasig-Tipton yearling auction. Seattle Slew was foaled at Ben Castleman's White Horse Acres Farm near Lexington, Kentucky. Hill and his wife, Sally, had met the Taylors through the horse business. In partnership, they bought 13 prospects, including Seattle Slew, who was sold for $17,500 (equivalent to $77,000 in 2015). They named him for the city of Seattle and the sloughs which loggers once used to transport heavy logs. Karen felt that the spelling of slough—a slow-moving channel of the Pacific Northwest—would be too hard for people to remember, so the spelling was changed to Slew. A later co-owner was Glenn Rasmussen, the accountant for the equine partnerships.[2]

Seattle Slew's owners sent the colt to Billy Turner, a friend and former steeplechase rider who had trained horses seasonally in Maryland since the early 1960s. Based at Belmont Park in the mid-1970s, Turner accepted Seattle Slew and another Taylor-Hill purchase and sent them to Andor Farm in Monkton, where his wife at the time, Paula, taught yearlings to be ridden.[3][4][5]

Seattle Slew made his first start in a six-furlong maiden race on September 20, 1976, the fifth race at Belmont Park on Long Island, New York. The big, nearly black colt was bet down to the 5–2 favorite. He gave the public its first look at what was later called his "war dance" (his habit of tiptoeing on the track before his races) and won by five lengths. Seattle Slew started only twice more as a two-year-old, winning an allowance race on October 5, 1976 by 3½ lengths and the one-mile Champagne Stakes 11 days later by 9¾ lengths in a fast 1:342⁄5.[6] Despite starting just three times, Seattle Slew was named Champion 2-Year-Old of 1976.

Turner scheduled three races for Seattle Slew leading up to the Kentucky Derby.[3] His first start as a three-year-old came on March 9, 1977, when he set a seven-furlong track record at Hialeah Park Race Track in winning an allowance race by nine lengths. On March 26, Seattle Slew won the Flamingo Stakes by four lengths in the third-fastest time in the stakes' 51-year history. On April 23, he completed his Kentucky Derby preparation with a 3¼-length victory in the Wood Memorial Stakes.

Seattle Slew went off as the odds-on 1-2 favorite in the 1¼-mile Kentucky Derby on May 7. A "speed horse" who normally broke well and went right to the lead, he swerved at the start and was taken up by jockey Jean Cruguet. However, Cruguet and Seattle Slew recovered and got to the lead, dueling with For the Moment for the first mile of the race. At the top of the stretch, Seattle Slew pulled away to win by 1¾ lengths over Run Dusty Run.

Two weeks later, in the 13⁄16-mile Preakness Stakes, Seattle Slew faced a new rival in multiple-stakes-winner Cormorant. Many handicappers believed the predicted speed duel with Cormorant would jeopardize the Derby winner's chances; Andrew Beyer picked Cormorant to win in his Washington Post column. Seattle Slew outstayed Cormorant, holding off Iron Constitution to win by 11⁄2 lengths.

The Belmont Stakes was a coronation for the Triple Crown champion, who won by four lengths before a large, enthusiastic crowd. He became the tenth American Triple Crown winner and (with his nine-for-nine record) was the first Triple Crown winner to finish the series undefeated.

After the Triple Crown, Seattle Slew was sent to Hollywood Park Racetrack, which offered a $400,000 purse to lure him to run in the Swaps Stakes on July 3, 1977. In the Swaps, Seattle Slew (who normally broke on the lead) was unable to get to the front. Jockey Bill Shoemaker sent J.O. Tobin (whom Seattle Slew had defeated in the Preakness) to the lead. J.O. Tobin set fast early fractions for a 1¼-mile race – 22.40 for the first quarter-mile, 45.40 for the half, 1:09.20 for six furlongs and 1:33.60 for the mile. Seattle Slew could not keep up and tired badly in the stretch, finishing fourth, 16 lengths behind J.O. Tobin, who won by eight lengths in 1:58.40, less than half a second off the American record for the distance at that time. After this loss, rest and physical problems sidelined Seattle Slew for almost a year. Despite the season-ending loss, however, he was honored at year's end as champion three-year-old and the Eclipse Award for American Horse of the Year.[7]

In early 1978, Seattle Slew was stabled at Hialeah and was expected to make three starts in Florida before contesting the one-mile Metropolitan Handicap in New York. In Florida, the horse (who had recovered from a cough as a three-year-old) took a turn for the worse in January. He stopped eating, occasionally broke into hours-long sweats and sometimes fell when he tried to stand. The cause was a collapsed left jugular vein. He fought off the life-threatening condition and returned to the races in May. Although veterinarians were concerned for his life and had suggested that he would never race again, Slew made it back to the races on a sloppy track at Aqueduct. By that time, Billy Turner had been replaced by Doug Peterson as his trainer. Seattle Slew won that allowance race at Aqueduct by 8½ lengths and won another seven-furlong allowance by six lengths at Saratoga Race Course in August. In preparation for a matchup against the 1978 Triple Crown winner Affirmed, Seattle Slew was sent to the Meadowlands for a night race, the Paterson Handicap. He lost to Dr. Patches in a major upset. Jean Cruguet lost his mount after that race, after expressing doubt if the horse was sufficiently trained.[8]

In the Marlboro Cup, the first matchup of two Triple Crown winners, Seattle Slew was not the favorite (for the only time in his career). Angel Cordero, Jr. took the reins as his new jockey Affirmed was the 1–2 favorite, and Seattle Slew was the 2–1 second choice. Affirmed's arch-rival Alydar was scheduled to run, but he was scratched the week before the race.

Affirmed and Seattle Slew were both speed horses. Seattle Slew broke on top and stayed there into the homestretch. Cordero took him away from the rail off the final turn; Affirmed came up on him, but Seattle Slew responded to beat Affirmed by three lengths in the time of 1:45.80 for 11⁄8 miles, .40 second off the track record set by Secretariat. Two weeks later, he won the 1¼-mile Woodward Stakes over Exceller by four lengths.

In October, Seattle Slew and Affirmed met again in the 1½-mile Jockey Club Gold Cup at Belmont, which was televised nationally on the CBS network. Affirmed's trainer, Laz Barrera, did not want Seattle Slew to get an easy lead and dictate the pace as he did in the Marlboro Cup, so Barrera also entered a "rabbit" (Life's Hope) in an attempt to tire Slew. Barrera's plan was compromised; Seattle Slew set a blistering pace, chased by Affirmed and Life's Hope. "Slew" drew away; Affirmed's saddle then slipped, eliminating him from contention (he finished 5th). Seattle Slew ran in fractions of 22.60 for the first quarter, 45.20 for the half and 1:09.40 for three-quarters – very fast early times for a long race.

Sitting far back, Willie Shoemaker on Exceller took advantage of the fast pace. Exceller made a strong move on the far turn and saved ground by moving inside Seattle Slew as the tiring horse bore out turning for home. Exceller took the lead at the top of the stretch, but Seattle Slew fought back and lost by a nose in a photo finish. This stretch run is still remembered as among the all-time best, ranking with Sunday Silence and Easy Goer's Preakness in 1989 and the battles between Affirmed and Alydar. Despite the defeat, many analysts considered this to be Seattle Slew's greatest performance. Andrew Beyer (a Seattle Slew skeptic when the horse was a three-year-old) wrote for his lead, "Exceller won Saturday's Jockey Club Gold Cup. Seattle Slew was its hero."[citation needed]

Seattle Slew's last race was a victory under the high weight of 134 pounds (61 kg) in the Stuyvesant Handicap in November at Aqueduct Racetrack by 3¼ lengths. He retired with 14 wins in 17 races and earnings of $1,208,726. Seattle Slew was named Champion Older Horse in 1978 but lost the Horse of the Year balloting to the horse he defeated in the Marlboro Cup, Affirmed. He was elected to the National Museum of Racing and Hall of Fame in 1981.

Seattle Slew stood at stud at Spendthrift Farm in Lexington for seven years,[9] before moving to Three Chimneys Farm in Midway in 1985. He was the leading sire of 1984, when his son Swale (who died later that year) won the Kentucky Derby and Belmont Stakes. His other progeny include the talented, ill-fated 1982 champion two-year-old filly, Landaluce, Slew o' Gold (winner of the 1983 Eclipse Award for Outstanding Three-Year-Old Male Horse and the 1984 Eclipse Award for Outstanding Older Male Horse), 1992 Horse of the Year A.P. Indy (sire of 2006 Preakness Stakes winner Bernardini, and 2007 Belmont Stakes winner Rags to Riches) and the 2000 champion three-year-old filly Surfside. He is also the only Belmont Stakes winner to sire a Belmont Stakes winner: A.P. Indy, who in turn sired a Belmont Stakes winner (Rags to Riches).

A primary conduit for Seattle Slew's continuation of his male line has been through A.P. Indy. A.P. Indy has done well at stud in Kentucky, siring (among others) the 2003 Horse of the Year, Mineshaft. One of Seattle Slew's most successful grandsons is the California champion Lava Man (sired by Slew City Slew). Seattle Slew's son Slewacide was the broodmare sire of 2003 Kentucky Derby and Preakness Stakes winner Funny Cide. In 2006, Lava Man became the first horse to win the Santa Anita Handicap, Hollywood Gold Cup and Pacific Classic Stakes in the same year. Seattle Slew was also a leading broodmare sire, his daughters producing (among others) Cigar (leading North American money-earner of his day). Races in honor of his dam, My Charmer, include the My Charmer Handicap held at Florida's Calder Race Course annually and the My Charmer Stakes held at Kentucky's Turfway Park.

25 years to the day after he won the Kentucky Derby, Seattle Slew died in his sleep at age 28. He was buried whole, the highest honor for a winning race horse, in the courtyard at Hill 'N' Dale Farm near Lexington, Kentucky, with his favorite blanket and a bag of peppermints which he liked to eat.[11]Three Chimneys Farm erected a statue of Seattle Slew near the stallion barn in his honor. Since fellow Triple Crown winner and rival Affirmed had died the year before, he was the sole living Triple Crown winner.[12] At the horse's death, there were no living Triple Crown winners for the first time since Sir Barton won the first Triple Crown in 1919. This phenomena continued until American Pharoah's Triple Crown in 2015.

Smarty Jones (the first undefeated Kentucky Derby winner since Seattle Slew) now occupies his predecessor's former stall. In 2008 (when Big Brown was syndicated), racing fans wanted Big Brown to have the stall; Three Chimneys denied the request.

In 2014, Seattle Slew's great-great grandson, California Chrome, won the Kentucky Derby [13] and the Preakness.[14] California Chrome is the second Kentucky Derby winner in a row who is a sire-line descendant of Seattle Slew, following Orb in 2013.[15]